Investigations into the effects of aging on the dsposition of meperidine in man are being pursued using a GC-MS method for determining plasma and urine levels of unchanged drug and its N-demethylated metabolite. By simultaneous administration of meperidine and its deuterated stable labelled analog, the pharmacokinetics of two routes of administration under identical physiological conditions may be examined. Of particular interest is the relation of age to altered oral and intramuscular bioavailability, systemic clearance and distribution. Other studies are directed towards definition of the separate roles of altered pharmacokinetics and pharmacodynamics in the increased "sensitivity" of the elderly to the benzodiazepines. The rat and rabbit are being investigated as possible animal models of the disposition changes associted with aging. Additionally, receptor binding characteristics for the benzodiazepines are being investigated. Clinical studies are directed towards establishing a quantifiable, graded dose response relationship for the central activity of this class of drug with particular emphasis on power spectral analysis of the EEG and psychometric tests. The phenomenon of enzyme induction in the elderly is also being studied clinically with reference to the extent and the rate at which the induced state is achieved relative to young individuals, using propranolol and rifampicin as model interactive drugs.